Validation of the first step of the heuristic refinement method for the derivation of solution structures of proteins from NMR data

Abstract

A new method for the analysis of NMR data in terms of the solution structure of proteins has been developed. The method consists of two steps: first systematic search of the conformational space to define the region allowed by the initial set of experimental constraints, and second, the narrowing of this region by the introduction of aaditional constraint and optional refinement procedures. The search of the conformational space is guided by heuristics to make it computationally feasible. The method is therfore called the heuristic refinement method and is coded in an expert system called PROTEAN. The paper describe the validation of the first step of the method using an artificial NMR data set generated from the known crystal structure of sperm whale carbon monoxymyoglodin. It is shown that the initial search procedure yields a low-resolution structure of the myoglobin molecule, accurately reproducing its main topological features, and that the precision of the structure depend on the quality of the intial data set.